ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2018) 15 1.4 | DOI: 10.1530/ey.15.1.4

ESPEYB15 1 Pituitary and Neuroendocrinology New mechanisms (6 abstracts)

1.4 Disrupted-in-Schizophrenia-1 is essential for normal hypothalamic-pituitary-interrenal (HPI) axis function

Eachus H , Bright C , Cunliffe VT , Placzek M , Wood JD & Watt PJ


Department of Animal and Plant Sciences, University of Sheffield, Western Bank, Sheffield, UK


To read the full abstract: Hum Mol Genet 2017;26:1992-2005

Mutations in human DISC1 have been previously associated with mental illness, such as schizophrenia and depression. Moreover, DISC1 has been shown to be important in regulating CNS neurogenesis through the Wnt/β-catenin pathway. However the mechanism by which DISC1 causes mental illness is not known. In this elegant work, Eachus et al. used two homozygous mutant zebrafish lines to understand the role of disc1. The authors show that disc1 affects hypothalamic development by controlling the proliferation of Rx3-positive hypothalamic progenitors neurons, that give rise to SF1 and Pomc1 neurons. Mutations of disc1 lead to abnormal neuroendocrine differentiation, leading to decreased levels of cortisol after environmental stress. Hence this paper shows how developmental abnormalities of the hypothalamus, leading to endocrinopathies at early stages of development, lead to behavioral abnormalities in adulthood and places disc1 as a new key player in hypothalamic development in fish model. POMC neurones form an integral part of the central melanocortin system regulating feeding behaviour and POMC deficiency leads to obesity in humans. Hence, it will be interesting to see whether these fish have abnormal regulation of feeding besides their behavioural abnormalities. Further studies in humans carrying mutations in DISC1 show assess if these patients have HPA-axis abnormalities and if these biological mechanisms are evolutionarily maintained through different species.

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